MPTP, MPP+ and mitochondrial function

Life Sci. 1987 Feb 23;40(8):721-9. doi: 10.1016/0024-3205(87)90299-2.


1-Methyl-4-phenylpyridinium (MPP+), the putative toxic metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), inhibited NAD(H)-linked mitochondrial oxidation at the level of Complex I of the electron transport system. MPTP and MPP+ inhibited aerobic glycolysis in mouse striatal slices, as measured by increased lactate production; MPTP-induced effects were prevented by inhibition of monoamine oxidase B activity. Several neurotoxic analogs of MPTP also form pyridinium metabolites via MAO; these MPP+ analogs were all inhibitors of NAD(H)-linked oxidation by isolated mitochondria. 2'-Methyl-MPTP, a more potent neurotoxin in mice than MPTP, was also more potent than MPTP in inducing lactate accumulation in mouse brain striatal slices. Overall, the studies support the hypothesis that compromise of mitochondrial oxidative capacity is an important factor in the mechanisms underlying the toxicity of MPTP and similar compounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium
  • Animals
  • Brain / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Glycolysis / drug effects
  • In Vitro Techniques
  • Kinetics
  • Liver / metabolism
  • Mice
  • Mitochondria / drug effects*
  • Oxygen Consumption / drug effects
  • Pyridines / toxicity*
  • Pyridinium Compounds / toxicity*
  • Rats
  • Selegiline / pharmacology
  • Structure-Activity Relationship


  • Pyridines
  • Pyridinium Compounds
  • Selegiline
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium